Reverse transcription polymerase chain reaction is a laboratory technique combining reverse transcription of RNA into DNA and amplification of specific DNA targets using polymerase chain reaction. It is primarily used to measure the amount of a specific RNA. The main advantage of PCR is its sensitivity: only one strand of sample DNA is needed to detect a particular DNA sequence. It now has many uses including prenatal diagnosis, detection of mutated oncogenes and diagnosis of infections.

Bivalirudin is a competitive, direct thrombin inhibitor. It inhibits both free and clot-bound thrombin and thrombin-induced platelet aggregation. Thrombin enables fibrinogen conversion to fibrin during the coagulation cascade. So inhibition of fibrinogen conversion to fibrin inhibits thrombus development.

Achondroplasia is a common cause of dwarfism. It is caused by a mutation in fibroblast growth factor receptor 3 (FGFR3). In normal development FGFR3 has a negative regulatory effect on bone growth. In achondroplasia, the mutated form of the receptor is constitutively active and this leads to severely shortened bones. The effect is genetically dominant, with one mutant copy of the FGFR3 gene being sufficient to cause achondroplasia, while two copies of the mutant gene are invariably fatal. A person with achondroplasia thus has a 50% chance of passing dwarfism to each of their offspring. People with achondroplasia can be born to parents that do not have the condition due to spontaneous mutation. It occurs as a sporadic mutation in approximately 80% of cases (associated with advanced paternal age) or it may be inherited as an autosomal dominant genetic disorder.
People with achondroplasia have short stature, with an average adult height of 131 centimeters (52 inches) for males and 123 centimeters (48 inches) for females.

From the given physical findings (the difference in BP between the radial and femoral arteries), the most probable diagnosis is coarctation of the aorta.

Carbon monoxide has high affinity for haemoglobin and myoglobin resulting in a left-shift of the oxygen dissociation curve and tissue hypoxia. There are approximately 50 deaths per year from accidental carbon monoxide poisoning in the UK. In these circumstances, antidotal therapy to block alcohol dehydrogenase with ethanol or 4-MP alone is insufficient to treat the poisoning. Data suggest that a severe lactic acidosis needs initial correction and in this patient the most appropriate treatment would be IV fluids with bicarbonate to correct the metabolic acidosis. Haemodialysis may be required thereafter.

Urea breath test is the most sensitive test to determine if there has been RESOLUTION/ERADICATION of the infection with H. pylori. The best test for initial diagnosis would be EGD with biopsy.

Drug metabolism can be broadly classified into:
Phase I (functionalization) reactions: also termed non-synthetic reactions, they include oxidation, reduction, hydrolysis, cyclization and de-cyclization. The most common and vital reactions are oxidation reactions. (Of the given enzymes only Alcohol dehydrogenase is involved in phase I drug metabolism. Succinate dehydrogenase, is a vital enzyme involved in the Kreb’s cycle and the mitochondrial electron transport chain). They are mainly catalysed by Cytochrome P-450 enzyme.

Phase II (conjugation) reactions: occur following phase I reactions, they include reactions: glucuronidation and sulphate conjugation, etc. They are mostly catalysed by UDP-glucuronosyltransferase enzyme. Other phase II enzymes include: sulfotransferases, N-acetyltransferases, glutathione S-transferases and methyltransferases.

Superior vena cava (SVC) obstruction is an oncological emergency caused by compression of the SVC and is most commonly associated with lung cancer.

Some causes of the condition include:
1. Common malignancies: non small cell lung cancer, lymphoma
2. Other malignancies: metastatic seminoma, Kaposi’s sarcoma, breast cancer
3. Aortic aneurysm
4. Mediastinal fibrosis

Clinical features of SVC obstruction include:
1. Dyspnoea: most common
2. Swelling of the face, neck, and arms: conjunctival and periorbital oedema may be seen
3. Headache: often worse in the morning
4. Visual disturbances
5. Pulseless jugular venous distension

Management options are:
1. General: dexamethasone, balloon venoplasty, stenting
2. Small cell lung cancer: chemotherapy and radiotherapy
3. Non small cell lung cancer: radiotherapy

Type I interferons (IFNs) form a network of homologous cytokines that bind to a shared, heterodimeric cell surface receptor and engage signalling pathways that activate innate and adaptive immune responses.

Clostridium species do not present with an exfoliative skin rash. C. perfringens is a common aetiology in necrotizing infections (gas gangrene) as well as food poisoning, which often also includes diarrhoea. C. difficle causes diarrhoea. C. tetany and C. botulinum have neurotoxins that can lead to paralysis.

Idiopathic hypercalciuria presents with excess calcium in the urine without an apparent cause. Dietary modification is the first step in addressing this condition, however, because hypercalciuria increases the risk of developing renal stones and bone demineralisation, thiazide diuretics should be prescribed to increase calcium reabsorption when these symptoms are also present.

Major depression (MD) often occurs after MI and has been shown to be an independent predictor of poor cardiovascular (CV) outcome.

Results of a randomized trial confirm that the antidepressant sertraline can be used safely in patients with recent MI or unstable angina and is effective in relieving depression in these patients.

Adverse effects to note:
Sertraline – Diarrhoea (13-24%), Nausea (13-30%), Headache (20-25%),
Insomnia (12-28%)
Imipramine – ECG changes, orthostatic hypotension, tachycardia
Confusion, extrapyramidal symptoms (EPS), dizziness, paraesthesia, tinnitus
Flupentixol – seizures, irregular/fast heartbeat, increased sweating
Paroxetine – Hypertension, Tachycardia, Emotional lability, Pruritus
Venlafaxine – Abnormal vision (4-6%), Hypertension (2-5%), Paraesthesia (2-3%), Vasodilation (2-6%), Aneurism, Deep vein thrombophlebitis, Takotsubo cardiomyopathy

Leaking of cerebrospinal fluid from the dura is the most likely explanation for post-lumbar puncture headaches. It is thought that ongoing leak of cerebrospinal fluid (CSF) through the puncture site causes ongoing CSF loss, leading to low pressure. A post-LP headache is typically frontal or occipital and occurs within three days. It is normally associated with worsening on standing and improvement when lying down. Treatment in severe cases includes an epidural blood patch, but most resolve on their own.

Malingering is not considered a mental illness. In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), malingering receives a V code as one of the other conditions that may be a focus of clinical attention. The DSM-5 describes malingering as the intentional production of false or grossly exaggerated physical or psychological problems. Motivation for malingering is usually external (e.g., avoiding military duty or work, obtaining financial compensation, evading criminal prosecution, or obtaining drugs).

Malingering should be strongly suspected if any combination of the following factors is noted to be present: (1) medicolegal context of presentation; (2) marked discrepancy between the person’s claimed stress or disability and the objective findings; (3) lack of cooperation during the diagnostic evaluation and in complying with the prescribed treatment regimen; and (4) the presence in the patient of antisocial personality disorder (ASPD).

This patient is be pretending to be sick in order to get morphine.

The patient likely has celiac’s disease, but if she has been avoiding gluten, a biopsy may be negative. Even though a biopsy is the gold standard for diagnosis, she will need to re-introduce gluten into her diet prior to undergoing the biopsy.

Patients with a VTE within the previous three months, patients with AF and previous stroke or TIA or multiple other risk factors, and patients with a mitral valve replacement should be considered for bridging therapy.

The most appropriate bridging therapy in this case would be low-molecular-weight heparin (LMWH), with the last dose given not less than 24 hours prior to the procedure. Warfarin should be discontinued 5 days prior to the procedure. If the INR is still above 3 on the day prior to the procedure, vitamin K should be administered.

Charcot arthropathy is a progressive condition of the musculoskeletal system that is characterized by joint dislocations, pathologic fractures, and debilitating deformities. It results in progressive destruction of bone and soft tissues at weight-bearing joints. In its most severe form, it may cause significant disruption of the bony architecture.
Charcot arthropathy can occur at any joint; however, it occurs most commonly in the lower extremity, at the foot and ankle. Diabetes is now considered to be the most common aetiology of Charcot arthropathy.

A Mongolian spot can be present in new born babies which usually appears over the back and fades with time. There is nothing to worry about.

Downbeat nystagmus (DBN) suggests a lesion in the lower part of the medulla. Arnold-Chiari malformation usually presents with symptoms due to brainstem and lower cranial nerve dysfunction such as DBN.

Prostate cancer is the most common primary tumour that metastasises to the bone.

Most common tumours causing bone metastasis (in descending order):
1. Prostate (32%)
2. Breast (22%)
3. Kidneys (16%)
4. Lungs
5. Thyroid

Most common sites of bone metastasis (in descending order):
1. Spine
2. Pelvis
3. Ribs
4. Skull
5. Long bones

Ethylene glycol poisoning is the only poison listed that will cause dilation of the pupils whereas all the other listed conditions and poisons will present with small pupils other than in the case of Myotonic dystrophy wherein the patient will present with a cortical cataract.

History and CXR are suggestive of tuberculosis. Acid fast bacilli should be seen on microscopy to confirm the diagnosis.

Illness anxiety disorder (IAD) is a recent term for what used to be diagnosed as hypochondriasis, or hypochondrial disorder. People diagnosed with IAD strongly believe they have a serious or life-threatening illness despite having no, or only mild, symptoms.

Symptoms of IAD may include:
-Excessive worry over having or getting a serious illness.
-Physical symptoms are not present or if present, only mild. If another illness is present, or there is a high risk for developing an illness, the person’s concern is out of proportion.
-High level of anxiety and alarm over personal health status.
-Excessive health-related behaviours (e.g., repeatedly checking body for signs of illness) or shows abnormal avoidance (e.g., avoiding doctors’ appointments and hospitals).
-Fear of illness is present for at least six months (but the specific disease that is feared may change over that time).
-Fear of illness is not due to another mental disorder.

Charles Bonnet syndrome (CBS) involves visual hallucinations due to eye disease, usually associated with a sharp decline in vision. The phenomenon is seen in patients with moderate or severe visual impairment. It can occur spontaneously as the vision declines or it may be precipitated, in predisposed individuals, by concurrent illness such as infections elsewhere in the body.

It is not clear why CBS develops or why some individuals appear to be predisposed to it. It is particularly noted in patients with advanced macular degeneration. It has been suggested that reduced or absent stimulation of the visual system leads to increased excitability of the visual cortex (deafferentation hypothesis). This release phenomenon is compared to phantom limb symptoms after amputation.

CBS is much more common in older patients because conditions causing marked visual loss are more common in older people. However, it can occur at any age and has been described in children.
The prevalence is hard to assess due to considerable under-reporting, perhaps because patients frequently fear that it is a sign of mental illness or dementia. However, it is thought to occur in:
About 10-15% of patients with moderate visual loss.
Possibly up to 50% of people with severe visual loss.
Presentation:
The nature of the hallucination depends on the part of the brain that is activated. The hallucinations may be black and white or in colour. They may involve grids/brickwork/lattice patterns but are typically much more complex:

The hallucinations are always outside the body.
The hallucinations are purely visual – other senses are not involved.
The hallucinations have no personal meaning to the patient.
Hallucinations may last seconds, minutes or hours.
CBS tends to occur in a ‘state of quiet restfulness’. This may be after a meal or when listening to the radio (but not when dozing off).
Symptoms also have a tendency to occur in dim lighting conditions.
Patients may report high levels of distress, with some patients reporting anger, anxiety and even fear associated with the hallucinations.

Anti–Mi-2 antibodies are highly specific for dermatomyositis, but sensitivity is low; only 25% of patients with dermatomyositis demonstrate these antibodies. A positive antinuclear antibody (ANA) finding is common in patients with dermatomyositis, but is not necessary for diagnosis. Anti-Jo-1 antibodies are mostly associated with polymyositis. Anti Scl-70 antibodies and anti centromere antibodies are most commonly found in systemic scleroderma.

The patient is most likely to have Postpartum thyroiditis which goes through 2 phases; hypothyroid and a hyperthyroid phase.
The hyperthyroid phase of postpartum thyroiditis occurs between 2 and 10 months postpartum. Most commonly, it presents at 3 months. Symptoms more common in women with hyperthyroid postpartum thyroiditis include palpitations, fatigue, heat intolerance, and irritability/nervousness. The frequency of asymptomatic hyperthyroidism is 33%.
Untreated, the hyperthyroidism resolves spontaneously within 2–3 months. This phase is diagnosed by the combination of a low serum TSH concentration in the presence of thyroid peroxidase antibodies, in women who are TSH receptor antibody-negative. Free T4 levels are typically elevated but may be normal.
Treatment of hyperthyroidism, when necessary, is based on symptom severity and should be a joint decision of patient and physician. Beta-blockers such as propranolol are given to alleviate palpitations, irritability, and nervousness. The morbidity associated with treatment is the side effects of beta-blockade. The downside of withholding treatment is allowing the woman to remain symptomatic. Antithyroid medicines (thioureas) are not a potential treatment alternative, because the hyperthyroidism is caused by destructive thyroiditis resulting in the release of preformed thyroid hormone.

Elderly patients with severe hypothyroidism often present with variable symptoms that may be masked or potentiated by co-morbid conditions. Characteristic symptoms may include fatigue, weight gain, cold intolerance, hoarseness, constipation, and myalgias. Neurologic symptoms may include ataxia, depression, and mental status changes ranging from mild confusion to overt dementia.
Clinical findings that may raise suspicion of thyroid hormone deficiency include hypothermia, bradycardia, goitrous enlargement of the thyroid, cool dry skin, myxoedema, delayed relaxation of deep tendon reflexes, a pericardial or abdominal effusion, hyponatremia, and hypercholesterolemia.

The patient has a greatly reduced free T4 concentration, is hypothermic, unconscious and has evidence of associated heart failure. All of those support the diagnosis of profound hypothyroidism.

Pulsus paradoxus is defined as the exaggerated fall in systolic blood pressure during inspiration by greater than 10 mmHg. Cardiac tamponade is the classic cause of pulsus paradoxus. Kussmaul’s sign (a rise in the jugular venous pressure on inspiration) is mostly seen in constrictive pericarditis. Hypotension, muffled heart sounds and raised JVP can be seen in both conditions.

CADASIL is the most common form of hereditary stroke disorder. This case has a strong history of migraine with aura with stroke-like episodes, characteristic of CADASIL. Additionally, there is positive family history of migraine and early dementia but no other vascular risk factors like hypertension, diabetes, or hypercholesterolaemia, which all confirm the suspicion of CADASIL, an arteriopathy where there is thickening of the smooth muscle cells in the blood vessels.

N-acetylcysteine depletes glutathione reserves by providing cysteine, which is an essential precursor in glutathione production.

Glutathione within the liver can normally detoxify these minuscule quantities of NAPQI and prevent tissue damage.
N-acetylcysteine (NAC) is the mainstay of therapy for acetaminophen toxicity.

Paracetamol overdose:
The liver normally conjugates paracetamol with glucuronic acid/sulphate. During an overdose, the conjugation system becomes saturated leading to oxidation by cytochrome P450 (predominately CYP2E1) mixed-function oxidases. This produces a toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI).

Normally glutathione acts as a defence mechanism by conjugating with the toxin forming the non-toxic mercapturic acid. If glutathione stores run-out, the toxin forms covalent bonds with cell proteins, denaturing them and leading to cell death.

Other uses: In COPD, cystic fibrosis, and other lung conditions, nebulized NAC has mucolytic, anti-inflammatory, and antioxidant properties.